Risk factors and immunomodulators use in steroid-refractory checkpoint inhibitor pneumonitis

Background: Checkpoint inhibitor pneumonitis (CIP) that does not respond to corticosteroids is termed steroid-refractory CIP. We aimed to find risk factors of steroid-refractory CIP and evaluate the management strategies of immunomodulators (IMs).

Methods: Patients with CIP were identified between August 2019 and August 2022 retrospectively. Clinical characteristics, peripheral blood biomarkers, and radiologic images were collected.

Results: Among 1209 patients with solid tumor receiving programmed death (ligand)-1 antibody, 28 patients developed steroid-refractory CIP and 38 patients developed steroid-response CIP. Patients with steroid-refractory CIP had a higher proportion of previous interstitial lung disease (p=0.015) and grade 3-4 (p<0.001) at diagnosis. Otherwise, absolute neutrophil count (ANC), procalcitonin were higher and albumin was lower in steroid-refractory patients (ANC, p=0.009; procalcitonin, p=0.024; albumin, p=0.026). After multivariate analysis, grade 3-4 and higher ANC at diagnosis were confirmed to be independent risk factors for steroid-refractory CIP (grade, p=0.001; ANC, p=0.046). For grade 2 steroid-refractory CIP, additional IMs did not affect the prognosis (p=1.000). However, additional IMs reduced the risk of deterioration significantly in grade 3-4 steroid-refractory CIP (p=0.036).

Conclusions: Grade 3-4 and higher peripheral blood ANC at diagnosis are associated with higher risk of steroid-refractory CIP. The use of additional IMs improves the outcome of grade 3-4 steroid-refractory CIP. These results can offer new insights to the decision-making of CIP management.